The Transgenics and Genetic Constructs Shared Resource (TGCSR) during much of the current funding period provided three main services: (1) generation of transgenic mice by DNA injection in outbred, mixed inbred and inbred mouse strains; (2) culture and transfection of ES cells to generate "knockout" ES clones; and (3) production of "knockout" mice using genetically modified ES cells. On average, the TGCSR generated 17 novel mouse models per year, consisting of approximately 11 transgenic mouse lines from individual DNA constructs and 6 ES cell-derived mutant mouse lines. The TGCSR provided various other services, including rederivation of pathogen-infected transgenic mouse lines, cryopreservation of transgenic mouse embryos and sperm, assistance with husbandry and genotyping of transgenic mouse lines, and assistance with special surgeries or IV injections for experimental purposes. Recently, the TGCSR has been reorganized to maximize efficiency and expand services to Dartmouth investigators. Transgenic and Genetic Construct Shared Resource (TGCSR) provides the additional major services of genetic constructs using "recombineering" in E. coli and yeast, purifying DNA for genotyping mice or ES cells, performing PCR or Southern blotting to genotype mice or ES cells, and karyotyping ES clones. The TGCSR services start with planning a new mouse model and end with genetically modified animals, with no further labor from the investigator. These expanded, start-to-finish services will support the generation of new experimental models by Dartmouth investigators who are not molecular biologists in their labs. In order to more efficiently utilize resources and respond to current directives from the NCI requesting that cancer centers seek regional collaboration and combine utilization of shared resources whenever feasible, Morris Cotton Cancer Center has entered into an agreement with the Jackson Laboratory (JAX) to have the mouse embryo manipulation for the TGCSR done by the transgenic shared resource at JAX. All previously provided services that do not involve manipulation of mouse embryos will continue to be performed at NCCC by the TGCSR. Under this new arrangement, the TGCSR director will be the conduit for all communications between Dartmouth investigators and JAX, for providing reagents to JAX, billing investigators, and financially compensating JAX. The vast experience and resources of JAX in the area of mouse genetics will provide even better service for NCCC investigators, and, since JAX makes a direct delivery of pathogen-free mice to Dartmouth every week, the movement of transgenic mice will be efficient and convenient for all. By partnering with JAX, the world's foremost facility for mouse genetics, and by expanding our services to include genetic construct production, karyotyping, and genotyping, we will better serve NCCC investigators.